One hundred and nine samples comprising carcinomas, adenomas, dysplastic, inflamed and normal mucosa from patients with sporadic colon cancer and ulcerative colitis (UC) were analysed for c-Ki-ras mutations. DNA was extracted from archival paraffin-embedded material, amplified using the polymerase chain reaction (PCR) and the PCR products analysed using restriction enzyme digestion. Forty-two per cent (14/33) of the sporadic carcinoma controls contained Ki-ras codon 12 mutations in contrast to 24% (8/33) of ulcerative colitis carcinomas. A significantly higher c-Ki-ras mutation rate was observed in rectal carcinomas (72%) in comparison to colonic carcinomas (28%) in control patients (P less than 0.04), while the opposite was observed in UC patients. The difference between the incidence of c-Ki-ras mutations in rectal carcinomas in UC (9%) and in sporadic rectal carcinomas (72%) was also significant (P less than 0.01). This lower prevalence rate and different site distribution of c-Ki-ras mutations in UC carcinomas compared to sporadic carcinomas suggests that specific genetic differences may underlie the causation of carcinomas arising in these situations.
1 Homogenates of mucosa from human colon metabolize [3H]-prostaglandin E1 in the presence of nicotinamide adenine dinucleotide to 15-oxo prostaglandin E1 or 15-oxo, 13,14 dihydro prostaglandin E1. 2 Metabolic capacity of tissue from patients with active ulcerative colitis under treatment with sulphasalazine (0.021 +/- 0.004 nmol/Mg protein +/- s.e. mean) did not differ from mucosa of normal patients (0.02 +/- 0.004 nmol/mg protein) during 1 h incubation. 3 Sulphasalazine inhibits prostaglandin E1 metabolism by mucosal homogenates in a dose-dependent manner with an ID50 of 125 microM. Its therapeutically active metabolite, 5-aminosalicylic acid (2.6 mM) was without significant inhibitory activity. 4 Indomethacin inhibits prostaglandin E1 metabolism by colonic mucosa with an ID50 of 388 microM. 5 At present we cannot clearly relate the therapeutic benefit of sulphasalazine and its therapeutically active metabolite, 5-aminosalicylic acid, in ulcerative colitis to their effects on prostaglandin E synthesis or metabolism in vitro.
The output of trypsin and chymotrypsin was determined in 26 patients with ulcerative colitis and 8 with polyposis coli, each of whom had undergone total colectomy and ileostomy. Measurements were made in each subject over periods ranging from 3 to 8 days on a standard diet. The output of each enzyme was lower in the group with ulcerative colitis, but serial post-operative measurements suggested that this was due to the relatively poorer nutritional status of patients in this group, and no consistent difference was apparent between individuals in both groups whose ileostomy had been established more than one year before the measurements were made.
We analysed the clinical significance of ANCA in patients with ulcerative colitis. On either an indirect immunofluorescence assay or an ELISA with fixed neutrophils, 71% (25/35) of the patients were positive for ANCA. However, only half of them reacted with either cathepsin G or lactoferrin. Western blot assays revealed positive bands in 40% (10/25) of the antibody-positive patients. The sizes of the bands detected were ≈58, 47, 44, 40, and 28 kD. No significant correlation was found between the ANCA positivity and various variables, i.e. disease activity, extent of lesion, or treatment of the disease. The anti-cathepsin G and 28-kD positivity, however, significantly correlated with a refractory type of ulcerative colitis.
Series studies suggest that enteropathogenic microorganisms play a substantial role in the clinical initiation and relapses of ulcerative colitis (UC). Mannan-binding lectin (MBL) is an important constituent of the innate immune system, and deficiency of MBL has been reported to increase the overall susceptibility of an individual to infectious disease. This study was aimed to investigate the associations between polymorphisms of the MBL gene and UC. Recruited in this study were 108 Japanese patients with UC and 144 healthy control subjects. Polymorphism at codon 54 of exon 1 of the MBL gene was investigated by polymerase chain reaction based restriction fragment length polymorphism. In general, no significant difference in MBL polymorphism was found between UC patients and health controls. However, the frequency of A carriers was significantly higher in the relapsing cases than controls (Odds ration = 2.19, 95%CI, 1.10–4.34; p = 0.023), and similar tendency was also found in A/A genotype. In conclusion, the polymorphism at codon 54 of exon 1 of the MBL gene associated with the susceptibility to the relapsing phenotype of ulcerative colitis. It suggests that codon 54 A variants of MBL gene may have an increased risk for the flare-ups of UC.
A case is reported of papillary thyroid adenocarcinoma with cervical lymph node metastases in a young man who had presented earlier with severe total ulcerative colitis. The aetiological factors in the pathogenesis of papillary thyroid carcinoma are briefly reviewed and an association between this neoplasm and ulcerative colitis is suggested.
A case of sudden bilateral sensorineural deafness associated with active ulcerative colitis is reported. Evidence for an autoimmune basis for this condition is reviewed and the potential benefit of systemic corticosteroids emphasized. The condition may represent a recently recognized extra-intestinal complication of ulcerative colitis.
Patients with long-standing ulcerative colitis have an increased chance of developing a carcinoma of the colon, especially when the inflammatory process involves the entire colon, but no case of a carcinoid tumour of the colon occurring in a patient with ulcerative colitis has been reported.
Two cases of biopsy-proven ulcerative colitis are described, and both developed a leucoerythroblastic anaemia during the course of the acute illness. Despite intensive investigation for the presence of bone marrow infiltration, no neoplasm was demonstrated. The leucoerythroblastic anaemia remitted in each case on medical treatment of the ulcerative colitis. The possible mechanisms underlying the development of reversible leucoerythroblastic anaemia are discussed.
We report a patient with ulcerative colitis who underwent colectomy when aged 25 years for multifocal high grade dysplasia which had developed within 2 years of diagnosis, and only 5 1/2 years after his first symptoms. The implications of this case for the management of ulcerative colitis are discussed.
A panproctocolectomy and permanent ileostomy improves the quality of life of those suffering from ulcerative colitis. However, it is not known how the quality of life of patients who had this operation compares with that of the general population. The aim of this study was to measure the quality of life of these patients using a reliable and validated instrument, and to determine whether these patients enjoy a similar quality of life to the general population. Forty-nine consecutive patients (31 males and 18 females, median age 49 years), who had a panproctocolectomy with a permanent ileostomy for ulcerative colitis in one of three hospitals in Tayside, UK from 1992-1997, participated in the study. The median number of months (range) post-surgery was 29 (12-72). Participants answered a well-validated generic questionnaire on health-related quality of life: the new SF-36 version 2.0 (SF-36II). The results were then compared with population norms of similar age and gender, derived from the Third Oxford Healthy Lifestyle Survey and published by the Health Services Research Unit of the University of Oxford. The mean score difference between patient and population SF-36II scores (95% confidence intervals) were as follows: physical functioning (PF): -3.9 (-9.4...
Patients with longstanding chronic ulcerative colitis are “at risk” of developing colorectal cancer. Approximately 1 in 6 patients will die as a result of colorectal malignancy, which can often be difficult to detect using conventional “white light” colonoscopy. New endoscopic techniques and technologies including the use of dye sprays, “chromoendoscopy”, high magnification chromoscopic colonoscopy and recently chromoscopic assisted confocal laser scanning in vivo endomicroscopy have now been introduced to improve the diagnostic yield of intraepithelial neoplasia at screening colonoscopy. This review details the true “risk” of colorectal cancer complicating ulcerative colitis, discusses the objective evidence to support current endoscopic screening guidelines, and describes the imminent technological paradigm shift about to occur in the endoscopic management and detection of intraepithelial neoplasia.
AIM: To compare thromboembolism rates between hospitalized patients with a diagnosis of ulcerative colitis and other hospitalized patients at high risk for thromboembolism. To compare thromboembolism rates between patients with ulcerative colitis undergoing a colorectal operation and other patients undergoing colorectal operations.
We report the case of a 21-year-old man who was noted to have pneumomediastinum during an admission for an acute flare of ulcerative colitis. At that time, he was on maintenance treatment with azathioprine at a dose of 1.25 mg/kg per day, and had not received supplementary steroids for 9 mo. He had never received anti-tumor necrosis factor (TNF)α therapy. Shortly after apparently effective treatment with intravenous steroids and an increased dose of azathioprine, he developed worsening colitic and new respiratory symptoms, and was diagnosed with Pneumocystis jiroveci (carinii) pneumonia (PCP). Pneumomediastinum is rare in immunocompetent hosts, but is a recognized complication of PCP in human immunodeficiency virus (HIV) patients, although our patient’s HIV test was negative. Treatment of PCP with co-trimoxazole resulted in resolution of both respiratory and gastrointestinal symptoms, without the need to increase the steroid dose. There is increasing vigilance for opportunistic infections in patients with inflammatory bowel disease following the advent of anti-TNFα therapy. This case emphasizes the importance of considering the possibility of such infections in all patients with inflammatory bowel disease, irrespective of the immunosuppressants they receive...
A number of cutaneous changes are known to occur in the course of inflammatory bowel diseases (IBD), including pyoderma gangrenosum, erythema nodosum, perianal disease, erythematous eruptions, urticaria, and purpura. However, occurrence of skin manifestations prior to the development of ulcerative colitis is a rare occasion. Here, we report a case of ulcerative colitis associated with leukocytoclastic vasculitis in which the intestinal symptoms became overt 8 mo after the development of skin lesions.
We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn’s disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn’s disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases.
In ulcerative colitis (UC)-associated tumours, p53 gene mutations and p53 protein overexpression are frequently found in early stages, but the two types of alteration do not always coincide. To clarify this discrepancy, p53 mutations and expression of p53-associated molecules were analysed in UC-associated dysplasias by a combination of microdissection, polymerase chain reaction-direct sequencing and immunohistochemistry at the single crypt level. Mismatch of p53 protein overexpression (+)/mutation (−) or p53 overexpression (−)/gene mutation (+) was found in nine crypts in regenerative mucosa (19 crypts), in 27 in low-grade dysplasia (41), in one in high-grade dysplasia (5) and in 12 in invasive carcinomas (17). Regarding these mismatched crypts of the first type, significant increase in p16INK4A and Bax expression was found. The Ki-67 labelling index was depressed in such p53-diffusely positive lesions with the wild-type p53 gene, compared to their p53-diffusely positive and mutant type counterparts. p16INK4A was upregulated indirectly as part of the negative feedback, and increase in Bax, directly controlled by wild-type p53, indicates upregulation of apoptosis. No significant relation with p53-related gene products was detected with the p53 protein overexpression (−)/p53 mutation (+) mismatch. Therefore...
Background. Both plasma and mucosal levels of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) have been shown to be independently correlated with ulcerative colitis (UC), but their relationship with each other and to disease severity remains unclear. This study aims to evaluate the relationship between colonic mucosal and plasma levels of MMP-1 and TIMP-1 with each other and with the severity of ulcerative colitis (UC). Methods. Colonic mucosal lesions and venous blood samples were collected from 30 patients with UC and 15 normal subjects. Real-time reverse transcription-PCR and immunohistochemistry were used to determine colonic mucosal MMP-1 and TIMP-1 expression; ELISA was used to measure plasma levels of MMP-1 and TIMP-1. Results. Expression of colonic mucosal and plasma MMP-1 and TIMP-1 in patients with UC was significantly higher than that of controls (P < .05), and was positively correlated with disease severity (P < .05). Plasma MMP-1 and TIMP-1 levels were well correlated with their corresponding expression in colonic mucosa (P < .05, r = 0.805 and 0.908). Conclusion. Plasma MMP-1 and TIMP-1 levels reflect their colonic mucosal expression to some extent in patients with UC. Plasma MMP-1 and TIMP-1...
Ulcerative colitis is a chronic inflammatory disease of the colon with an increasing incidence worldwide. The medical management of this disease continues to expand as drugs to induce and maintain remission are sought to avoid the need for colectomy. This article will review the standard of care for the treatment of mild, moderate, and severe ulcerative colitis. The efficacy, optimal usage, and adverse events profile of agents such as 5-aminosalicylates, corticosteroids, azathioprine, and cyclosporine will be discussed and an algorithm for their use will be developed. Alternative and experimental therapies such as monoclonal antibodies, probiotics, and heparin will also be addressed.